Despite advances in hypertension prevention and treatment research, the prevalence of hypertension is high and increasing, while the proportions of hypertensive patients who are aware, treated, and controlled are low in populations, especially in low and middle income countries. There are limited data on the implementation of effective and affordable programs for hypertension control in these countries. We propose to conduct a cluster randomized trial to test whether a comprehensive intervention program within a national public primary care system will improve hypertension prevention and control among uninsured hypertensive patients and their families in Argentina. The proposed trial will recruit 1,888 study participants from 16 primary care clinics within a public primary care network in Argentina. Eight clinics with approximately 944 participants will be randomly assigned to the comprehensive intervention group and 8 clinics with similar participants to the usual care group. Patients with hypertension from the participating clinics and their adult family members will be enrolled. The comprehensive intervention, including health care provider education, a home-based intervention among patients and their families (lifestyle modification and home blood pressure [BP] monitoring) delivered by community health workers, and a mobile health intervention, will last for 18 months. BP and other indicators will be measured at baseline and months 6, 12, and 18 during follow-up using standard methods. The primary outcome is net change in systolic and diastolic BP from baseline to month 18 between the intervention and control groups among all study participants. The secondary outcomes are the proportion of hypertensive patients with adequate BP control (<140/90 mmHg or <130/80 mmHg if patient has diabetes or chronic kidney disease) and the cost-effectiveness of the intervention program. The proposed trial has 90% statistical power to detect a >/=2.0 mmHg reduction in systolic and a >/=1.6 mmHg reduction in diastolic BP at a two-tailed significance level of 0.05. It also has over 80% power to detect a 26% increase in hypertension control rates in hypertensive patients. We will disseminate the study findings and scale-up the proven effective intervention program to the entire network nationwide. We have assembled a multidisciplinary investigative team, which will partner with the public primary care network in Argentina to conduct this implementation research project. Although all individual components of the proposed intervention program have been documented to be effective in previous clinical trials, their combined effects on hypertension control in populations have not been demonstrated. This implementation research project has a high impact in public health, because it will generate urgently needed data on effective, practical, and sustainable intervention programs aimed at reducing BP-related disease burden. The results from the proposed study may be directly used in other primary care settings and healthcare systems in low and middle income countries for hypertension prevention and control. RELEVANCE: We propose to conduct a cluster randomized trial to test whether a comprehensive intervention program within a national public primary care system will improve hypertension prevention and control among uninsured hypertensive patients and their families in Argentina. The comprehensive intervention, including health care provider education, a home-based intervention for patients and their families (lifestyle modification and home blood pressure monitoring) delivered by community health workers, and a mobile health intervention will last for 18 months. This implementation research has a high impact in public health because it will generate urgently needed data on effective, practical, and sustainable intervention programs for the prevention and control of hypertension in low and middle income countries.